CAR T cells, often called “living drugs,” are engineered from a patient’s own immune cells to hunt down and kill cancer. Although CAR T cells have been a breakthrough treatment for patients with blood cancers, their effects can be short-lived, and they are not yet effective for all patients or for all cancer types. Drs. Debattama Sen and Robert Manguso are on a mission to make CAR T-cell therapy work better, for more people, and for longer.

Together they are investigating the rare CAR T cells that are especially powerful – those that can kill cancer cells over and over again, a phenomenon known as “serial killing.” The team created a new platform that tracks which specific CAR T cells kill which cancer cells. To kill a cancer cell, or initiate cell death, CAR T cells release a molecule called Granzyme B. When this happens, the “kiss of death” platform is activated and the cancer cell marks or tags the specific CAR T cell  that killed it. The more tags a CAR T cell picks up, the more potent it is.

By studying these high-performing CAR T cells and running large-scale genetic screens, Drs. Sen and Manguso aim to uncover what makes a CAR T cell a true cancer killer and how to engineer more of them. It’s a bold approach with the potential to boost CAR T-cell therapy for patients battling blood cancers and solid tumors.

Research Focus

CAR T-cell therapy, solid tumors, genetic screens

Projects and Grants

Engineering «serial killer» T cells to enhance CAR T-cell efficacy in solid tumors